Glatiramer acetate (GA) is a synthetic peptide mixture (relative molecular weight: 4700-11000 Daltons), a random polymer consisting of four kinds of amino acids: L-alanine, L-glutamic, L-tyrosine and L-lysine, with a length of 45-100 amino acids. The molar ratios of each kind of amino acids are approximately 0.392-0.462, 0.129-0.153, 0.086-0.100 and 0.300-0.374. This drug is manufactured by the Israeli TEVA pharmaceutical factory (TEVA) with a trade name of Copaxone®. It was approved for the treatment of multiple sclerosis by FDA in 1996, and there are two kinds of products, water needle and freeze-dried powder needle, both of which are administered by subcutaneous injection.
Glatiramer acetate is a copolymer with high continuity, the structure of the glatiramer acetate is as follows:(Glu,Ala,Lys,Tyr)x.xCH3COOH(C5H9NO4.C3H7NO2.C6H14N2O2.C9H11NO3)x.xC2H4O2  CAS-147245-92-9
For the manufacturers imitating the drug, the compositional differences between the imitation of glatiramer acetate and the control group of the glatiramer acetate can only be examined based on some of the inherent properties of the drug.
The difference between a sample and a commercial product (reference substance) is examined by gradient elution in an anion exchange liquid chromatography, a cation liquid chromatography and/or a reversed-phase liquid chromatography in the present invention based on the electric charge, polar or nonpolar character of the sample in different buffer solutions.
As the glatiramer acetate is a copolymer with high continuity, it is difficult to clarify the various components with only one separation method. A size exclusion method is used in the prior art for a simple separation and analysis (dividing a single peak into several components, and then collecting and analyzing the components). Thus, the prior art is very tedious. It is very necessary to develop an analytical method for an effective separation of the components of the glatiramer acetate.